Iaoe?iiaeueia Aeaaeai?y Iaoe Oe?a?ie

Iinoeooo o?c?ieia?? ?i. I. I. Aiaiiieueoey

O?e?iia A?oae?e Ieoaeeiae/

OAeE 612.822:577.3

E+-aeoeaiaaia Na+-ea?iaaia eae??aa i?ia?aei?noue o iaia?ai? i??ai?aeieo
iae?ii?a iiceo uo?a

03.00.02 — a?io?ceea

Aaoi?aoa?ao aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

eaiaeeaeaoa a?ieia?/ieo iaoe

Ee?a — 1999

— 17 —

Aeena?oaoe??th ? ?oeiien

?iaioa aeeiiaia o a?aeae?e? o?ceei-o?i?/ii? a?ieia?? ee?oeiieo iaia?ai

?inoeoooo o?c?ieia?? ?i. I. I. Aiaiiieueoey IAI Oe?a?ie

Iaoeiaee ea??aiee: aeaaeai?e IAI Oe?a?ie, aeieoi? a?ieia?/ieo iaoe

E?eooaeue Ieaa Ieaenaiae?iae/

caa. a?aeae?eii o?ceei-o?i?/ii? a?ieia?? ee?oeiieo iaia?ai ?inoeooo
o?c?ieia?? ?i. I. I. Aiaiiieueoey IAI Oe?a?ie

Io?oe?ei? iiiiaioe:

Aeieoi? a?ieia?/ieo iaoe, i?ia?aeiee iaoeiaee ni?a?ia?oiee a?aeae?eo
caaaeueii? o?c?ieia?? ia?aiai? nenoaie Aanaeianueeee Ieeiea Na?a?eiae/
(?inoeooo o?c?ieia?? ?i. I. I. Aiaiiieueoey IAI Oe?a?ie)

Eaiaeeaeao a?ieia?/ieo iaoe, caa. a?aeae?eii iae?io?i?? A?iiaeue?aeo
I?ia Aa?iai?aia (?inoeooo a?io?i?? ?i. I. A. Iaeaae?ia IAI Oe?a?ie)

I?ia?aeia onoaiiaa: Iaoe?iiaeueiee Oi?aa?neoao ?i. O. A. Oaa/aiea,
a?ieia?/iee oaeoeueoao, eaoaae?a a?io?ceee, i. Ee?a

Caoeno a?aeaoaeaoueny » 22 » /a?aiy 1999 ?. i » 14-00 » aiaeei? ia
can?aeaii? niaoe?ae?ciaaii? a/aii? ?aaee Ae-26.198.01 i?e ?inoeooo?
o?c?ieia?? ?i. I. I. Aiaiiieueoey IAI Oe?a?ie ca aae?anith: 252024, i.
Ee?a, aoe. Aiaiiieueoey 4.

C aeena?oaoe??th iiaeia iciaeiieoenue o a?ae?ioaoe? ?inoeoooo o?c?ieia??
?i. I. I. Aiaiiieueoey IAI Oe?a?ie ca aae?anith: 252024, i. Ee?a, aoe.
Aiaiiieueoey 4.

Aaoi?aoa?ao ?ic?neaiee » 21 » o?aaiy 1999 ?.

A/aiee nae?aoa?

niaoe?ae?ciaaii? a/aii? ?aaee

aeieoi? a?ieia?/ieo iaoe Ni?ie?ia-Ia??ia C. I.

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE

Aeooaeuei?noue oaie. Caoaeaeaiiy u?eueii niaeiaaieo oeaio?aeueieo
iae?ii?a noi?iaiaeaeo?oueny cia/iei ca?eueoaiiyi ciai?oiueiee?oeiii?
eiioeaio?aoe?? eae?th. I?aeaeuaiiy ciai?oiueiee?oeiii? eiioeaio?aoe?? K+
a iaaeao o?c?ieia?/iiai ae?aiaciio a?ae 2 — 4 iI (Sykova, 1983; Croning
et al., 1995) aei 5 — 9 iI aeeeeea? iaia?aiio aeaiiey?ecaoe?th
(Traynelis & Dingledine, 1988), ca?eueoo? aiie?ooaeo EPSP ?
iiioeyoe?eieo iioaioe?ae?a ae?? (Hablitz & Lundervold, 1981), ni?ey?
iioe?aiith caoaeaeaiiy o a?aeiia?aeue ia aeaeo?inoeioeyoe?th (Somjen &
Giacchino, 1985; Ludvig et al., 1996). I?e iaoieia?yo a oeaio?aeuei?e
ia?aia?e nenoai? eiioeaio?aoe?y eae?th aeinyaa? cia/ii aeueo cia/aiue.
A?oa??aeueia a?iien?y iiaea aeeeeeaoe i?aeaeuaiiy eiioeaio?aoe?? eae?th
aei ??aiy 15 iI ? aeua (Kirshner et al., 1975). A?aecia/ai? aeiaaeee
a?iien?? iiceo, i?e yeeo eiioeaio?aoe?y ciai?oiueiee?oeiiiai eae?th
ca?eueoo?oueny a?eueo ??cei, ? iiaea aeinyaaoe ??ai?a, ui ia?aaeuothoue
50 iI (Hansen, 1985). I?aeaeuaiiy eiioeaio?aoe?? eae?th iiaea iaoe ??cia
ooieoe?iiaeueia cia/aiiy a caeaaeiino? a?ae oiai, yeei /eiii iaia?aii?
iaoai?cie, ui i?aeo?eiothoue iioaioe?ae niieith, ?aaaothoue ia ci?ie
a?aae??ioa oeeo ?ii?a. I?ia?aei?noue aeayeeo K+ eaiae?a ?aaoeth?oueny
iai?aai?/ieie ?iiaie. Eaeueoe?e-aeoeaiaai? eae??a? eaiaee IK(Ca) (Brown
& Griffith, 1983) oa IAHP (Alger & Nicoll, 1980) aeoeaothoueny
aioo??oiueiee?oeiiei Ca2+, a oie /an ye IK(Na) (Kameyama et al,. 1984)
aeoeao?oueny ci?iaie o aioo??oiueiee?oeii?e eiioeaio?aoe?? ?ii?a Na+.
?niothoue oaeiae aeai? i?i caeaoi?noue i?iieeath/eo ?ii?a iiaeoethaaoe
e?iaoeeo K+ eaiae?a oa ?o i?ia?aei?noue (Hoshi et al., 1990; Dale,
1993), aeia?a iienaia ?ieue aioo??oiueiee?oeiii? eiioeaio?aoe?? iao??th
a ?aaoeyoe?? i?ia?aeiino? eaee?aeo eaiae?a ?c aioo??oi?i aei?yieaiiyi
(Harvey & Ten Eick, 1989). Iaie aeyaeaiee iaoai?ci eae??ai?
i?ia?aeiino?, yeee aaciina?aaeiuei ea?o?oueny ?iiaie K+ ? Na+. Oeae
iaoai?ci eiio?ieth? cia/io /anoeio iaia?aiii? i?ia?aeiino? i??ai?aeieo
iae?ii?a iiaeeco iioaioe?aeo niieith ? iiaea ?noioii aieeaaoe ia
?aaeoe?th u?eueii oiaeiaaieo i??ai?aeieo iae?ii?a o a?aeiia?aeue ia
ci?ie ciai?oiueiee?oeiii? eiioeaio?aoe?? eae?th, aeeeeeai?
iae?iiaeueiith aeoeai?noth.

Iaoa aeine?aeaeaiiy. Iaoith ?iaioe aoei aeaoaeueia aeine?aeaeaiiy
aeanoeainoae K+- aeoeaiaaiiai no?oio ieaciaoe/ii? iaia?aie i??ai?aeieo
iae?ii?a iiceo uo??a, aea/aiiy eiai iniiaieo aeaeo?io?c?ieia?/ieo ?
oa?iaeieia?/ieo oa?aeoa?enoee, a oaeiae c’ynoaaiiy iaoai?ci?a ?aaoeyoe??
oe??? i?ia?aeiino? ?iiaie K+ ? Na+.

Caaaeaiiy aeine?aeaeaiiy. Aeei?enoiaoth/e iaoiae aioo??oiueiee?oeiii?
ia?ooc?? a eiio?ao?aoe?? «oe?ea ee?oeia» a eiia?iaoe?? c oaoi?eith
?iioeuenii? ci?ie ?ic/eio, e?iaoe/ii ?icae?eeoe K+- aeoeaiaaiee no?oi ia
ie?ai? eiiiiiaioe. I?iaanoe oa?iaeieia?/iee aiae?c K+ — aeoeaiaaiiai
no?oio c iaoith ii??aiyiiy iniiaieo oei?a iioaioe?aeea?iaaieo K+ eaiae?a
c eaiaeaie, ui eaaeaoue a iniia? K+ — aeoeaiaaii? i?ia?aeiino?
i??ai?aeieo iae?ii?a a?iieaiia.

C’ynoaaoe iniaeeaino? iioaioe?aecaeaaeiino? K+- aeoeaiaaiiai no?oio ?
anoaiiaeoe eiai ?iiio i?e?iaeo. Aea/eoe ?ieue ciai?oiueiee?oeiiiai Na+ a
oi?aae?ii? i?ia?aei?noth, ui aeoeao?oueny eae??i.

Aeine?aeeoe oaiia?aoo?io caeaaei?noue e?iaoeee aeoeaaoe?? IK.

I?iaiae?coaaoe iiaeeeaa cia/aiiy IK a oi?ioaaii? ?aaeoe?? i??ai?aeieo
iae?ii?a o a?aeiia?aeue ia no?eaeiiiae?ai? ci?ie ciai?oiueiee?oeiiiai
eae?th, aeeeeeai? aeoeai?noth non?aei?o iae?ii?a.

Iaoeiaa iiaecia ?iaioe. Aeyaeaiee ?ai?oa iaa?aeiiee iaoai?ci eae??ai?
i?ia?aeiino?, yeee aaciina?aaeiuei aeoeao?oueny ?iiaie K+, a ea?o?oueny
?iiaie K+ ? Na+. Oeae iaoai?ci aeanoeaee i??ai?aeiei iae?iiai a?iieaiia
? ei?e, iaeiae i?aeoe/ii a?aenooi?e a iae?iiao caaei?o ei??ioe?a
nieiiiai iiceo oa iae?iiao iici/ea. Io?eiai? a ?iaio? ?acoeueoaoe
aeicaieythoue c?iaeoe i?eiouaiiy, ui ?iie iao??th ? eae?th a?athoue
?ieue niaoeeo?/ieo ?aaoeyoi??a, a?aeiia?aeaeueieo ca noai a?eueoi?
/anoeie i?ia?aeiino? niieith i??ai?aeieo iae?ii?a.

Oe? aeai? cia/ii aeiiiaiththoue oyaeaiiy, ui ?nioaaee ?ai?oa, i?i
eae??aee no?oi «aeoieo», aai no?oi niieith (Storm, 1990). Aeei?enoaia a
?iaio? oaoi?ea ci?ie ?ic/eio ca aeiiiiiaith i’?cie?enoaea, ui ? ia
aeaiee iiiaio iaea?eueo oaeaeeith na?aae iaoiae?a aea/aiiy ?aaeoe?e
aaii?no-?aoeaioi? a ia??aiiaaaeieo oiiaao, aeicaieeea e?iaoe/ii
?icae?eeoe i?ia?aei?noue, ui aeoeao?oueny ieoo?ai ? yaey? niaith
«cae/aeiee» aeo?e ? i?ia?aei?noue, ui eaaeeoue a iniia? aeoeaaoe?? IK.
I?iaaaeaiee oa?iaeieia?/iee aiae?c IK. Ca aeiiiiiaith no/anieo
aeaeo?io?c?ieia?/ieo iaoiae?a aea/aiee aieea ciai?oiueiee?oeiiiai Na+ ia
IK, aeine?aeaeaia iioaioe?aecaeaaei?noue iiaiai no?oio, anoaiiaeaia eiai
?iiia i?e?iaea.

Oai?aoe/ia oa i?aeoe/ia cia/aiiy ?iaioe. Io?eiai? ?acoeueoaoe
aeicaieythoue ?noioii ?icoe?eoe oyaeaiiy i?i ?aaeoe?th i??ai?aeieo
iae?ii?a ia ??ce? ci?ie ciai?oiueiee?oeiii? eiioeaio?aoe?? eae?th a OeIN
uo??a. Iia? aeai? c oeueiai ieoaiiy ? aaaeeeaeie aeey oi?ioaaiiy a?eueo
iiaiiai oyaeaiiy i?i o?c?ieia?/io ?ieue ciai?oiueiee?oeiiiai eae?th a
?aaoeyoe?? ooieoe?e ia?aiai? nenoaie, oaeeo ye iae?iiaeueia caoaeaeaiiy
? i?aeee?oeii? aca?iiae??, a oaeiae a ooieoe?iioaaii? ae?aeueieo ee?oei.

Iia?eueia ca’ycoaaiiy iao??th c iaia?aiieie no?oeoo?aie, ui
niinoa??aa?oueny a oiiaao i?yii? ?a?no?aoe?? ? ne?aeia? aoaeoe i?ney
eiai aeaeaeaiiy aeicaieythoue ?icoe?eoe no/ani? oyaeaiiy i?i i?ioeane,
ui a?aeaoaathoueny a no?oeoo?? eaiaeo.

Aeine?aeaeaiiy aieeao aeieaoi??a iioaioe?aeea?iaaieo E+ eaiae?a ia E+-
aeoeaiaaiee eae??aee no?oi iiaea iineoaeeoe ii/aoeii iiooeo iiaeo oeyo?a
oa?iaeieia?/iiai aieeao ia iae?iiaeuei? iaoai?cie, iia’ycai? c eae??aith
aeoeai?noth, oae? ye ai?eain?y oa ?oai?y.

Iniaenoee aianie. Aaoi?ii iniaenoi aoee aeeiiai? an? aeaeo?io?c?ieia?/i?
aenia?eiaioe. O ?ic?iaoe? eiioeaioe?? aeine?aeaeaiue aeoeaio o/anoue
i?eeiaee ni?aaaoi?e ae?oeiaaieo ?ia?o.

Ai?iaaoe?y ?iaioe. Iniiai? iieiaeaiiy ?iaioe aoee aeieeaaeai? ?
iaaiai?ai? ia: 2-ii ui??/iiio c’?cae? ?a?iiaenueeiai Iae?iiaoeiaiai
Oiaa?enoaa (1996, No?anao?a, O?aioe?y); 26-iio ui??/iiio c’?cae?
Iae?iiaoeiaiai Oiaa?enoaa (1996, Aaoeiaoii, NOA); 4-iio i?aeia?iaeiiio
oa?iaeieia?/iiio eiia?an? «Eae??a? Eaiaee», (1996, Aaoeiaoii, NOA);
5-iio ui??/iiio c’?cae? ?c?a?euenueeiai Iae?iiaoeiaiai Oiaa?enoaa (1996,
Aeeao, ?c?a?eue); 1-iio aa?iaii-oe?a?inueeiio neiiic?oi? “Potassium
Channels Gene Expression“ (Ee?a, 1997); 27-iio ui??/iiio c’?cae?
Iae?iiaoeiaiai Oiaa?enoaa (1997, Iiaee I?eaai, NOA); Eiia?an?
O?c?ieia?/iiai Oiaa?enoaa Aaeeeia?eoai?? (1998, Naooaaiioii,
Aaeeeia?eoai?y).

Ioae?eaoe??. Ca ?acoeueoaoaie ?iaioe iioae?eiaaii o?e noaoo? oa oace
oanoe aeiiia?aeae.

No?oeoo?a oa ianya aeena?oaoe??. Aeena?oaoe?y neeaaea?oueny c? anooio,
iaeyaeo e?oa?aoo?e, iaoa??ae?a oa iaoiae?a aeine?aeaeaiiy, ?acoeueoao?a
aeine?aeaeaiue, iaaiai?aiiy ?acoeueoao?a, aeniiae?a oa nieneo
aeei?enoaieo aeaea?ae c? 234 iaeiaioaaiue. ?iaioa aeeeaaeaia ia 121
noi??ioe? oa ?ethno?iaaia 23 ?enoieaie.

IAOIAeEEA AeINE?AeAEAIUe

Ia’?eo aeine?aeaeaiue. Aeine?aeaeaiiy i?iaiaeeeeny ia ?cieueiaaieo
iae?iiao a?iieaiia, ei?e, iae?iiao caaei?o ei??ioe?a nieiiiai iiceo oa
iae?iiao Io?e?i’? iici/ea uo??a.

Na?aeiaeenioe?eiaai? iae?iie a?iieaiia iaea?aeoaaee ca aeiiiiiaith
i?eeii?a, iiae?aieo iienaiei ?ai?oa (Kiskin et al., 1990). 12 –
14-aeaiieo uo??a e?i?? A?noa? oaeaeei aeaeai?ooaaee aac canoinoaaiiy
aianoac??. ?c iane iiceo aeae?eyee a?iieaii, yeee ??caee ia c??ce
caaoiaoee 300-500 iei a ?ic/ei?, yeee i?noea a nia? (a iI ia 1 e): NaCl
– 150; ENl – 5; NaI2?I4 – 1.25; NaN12 – 2; MgN12 – 2; NaINI3 – 26;
aetheico – 20. I?a?ieoaaoe?y c??c?a o oaeiio ?ic/ei? o?eaaea 30 oa i?e
e?iiaoi?e oaiia?aoo??. Aiceiaoe/ia ia?iaea i?iaiaeeeany a iiae?aiiio
?ic/ei?, aea c? cieaeaiith aei 0.5 iI eiioeaio?aoe??th Na2+ oa
aeiaeaiiyi 0.5 i?ioaace c Aspergillus oryzae (“Sigma”, NOA). ?ieoaaoe?y
a ?ic/ei? c oa?iaioii o?eaaea 30 – 40 oa i?e 32 iC. Iio?i c??ce
ia?aiineee aei ?ic/eio aac oa?iaioo oa c ii?iaeueiith eiioeaio?aoe??th
Na2+; i?ioyaii 6 – 8 aiae aiie neoaoaaee aeaea?aeii ?cieueiaaieo
iae?ii?a. O i?ioean? ?cieyoe?? oa ianooiii? ?ieoaaoe?? ?ic/eie iino?eii
iane/oaaeeny noi?ooth 95 % I2 oa 5 % NI2, ui caaacia/oaaei i?aeo?eiaiiy
?I ia ??ai? 7.4. Aeey aeenioe?aoe?? ee?oei c??c ia?aiineee a ?ic/ei,
yeee i?noea o nia? (a i?e?iieyo ia 1 e): NaN1 – 150; EN1 – 5; NaN12 – 2;
IgN12 – 2; IA?AS – 10; ?I aeiaiaeeany aei 7.4 aeiaeaiiyi NaII.
Iiiaeeiie? i??ai?aei? e?oeie ?ciethaaeeny ?c cii NA1 ? NAC. I?ney
?cieyoe?? oae? ee?oeie iiaee aooe aeei?enoai? aeey a?aeaaaeaiiy i?ioyaii
2 – 4 aiae. I?e ?ciethaaii? iae?ii?a ei?e i?ioeaaeo?e aeae?eaiiy ee?oei
? ?ic/eie aeey ia?iaee aoee o? ae. Iae?iie caaei?o ei??ioe?a nieiiiai
iiceo ?ciethaaee ii iaoiaeeoe?, iiae?ai?e iienaiei ?ai?oa (Krishtal et
al. 1988). Iae?iie Io?e?i’? iici/ea ?ciethaaee ca iaoiaeeeith,
iiae?aiith iienai?e ?ai?oa (Panchenko et al., 1993).

I?eeeaaeaiiy oa?iaeieia?/ii aeoeaieo ?a/iaei. Ci?ia ?ic/ei?a oa
aie?eaoe?y oa?iaeieia?/ieo aaaio?a aeeiioaaeeny ca aeiiiiiaith iaoiaeeee
oaeaeei? o?enaoe?? eiioeaio?aoe?? c aeei?enoaiiyi oaeaee?nii?
i?e?iia?ooc?eii? nenoaie. Inoaiiy aacoaaeany ia iiceoe?iioaaii?
eai?ia?ieo no?oi?a ?ic/ei?a ca aeiiiiiaith i’?ciaeaeo?e/iiai ea?oth/iai
i?eno?ith (Franke et al., 1987; Colquhoun et al., 1992)‘‘. Aeainoaieuei?
i?iaoee aeey aie?eaoe?e ae?iaeyeeny c o?oai/ie ?-neea ?c ciai?oi?i
ae?aiao?ii 2 ii (“Clark Electromedical Instruments”, Aaeeea A?eoai?y);
i?ney aeoyaoaaiiy ae?aiao? e?i/eea noaiiaea aeecueei 150 iei. I?iaoea
aeey aie?eaoe?e i?e?aeioaaeany aei i’?ciaeaeo?e/iiai ia?aieea/a
(?810-30, “Physik Instrumente”, O?I). Ciai?oi? ?ic/eie iinoa/aeeny a
eiaeiee c aeaio noaie?a i?iaoee ca aeiiiiiaith eiio?ieueiaaiiai
eiii’thoa?ii ?ioaoe?eiiai i?eno?ith c i’?ciia?aieeaiiyi (“E?eay”,
Oe?a?ia), yeee iaa 16 ?aca?aoa??a. Iaeei eaiae aeei?enoiaoaaee aeey
i?eeeaaeaiiy oano-?ic/eio, a ae?oaee – aeey i?eeeaaeaiiy ?iaeeoa?aioiiai
?ic/eio. Iaaeoiaeaeaiiy eiaeiiai c ?ic/ei?a ea?oaaeiny ca aeiiiiiaiii
?iaeea?aeoaeueiiai eeaiaia ? oaeiae eiio?iethaaeiny eiii’thoa?ii. E??i
oiai, any eaia?a iino?eii ia?oocoaaeany eiio?ieueiei ?ic/eiii aeey oiai,
uia caiia?aoe iaeiie/aiith oa?iaeieia?/ieo

?en. 1. I?eioeei ae?? oaeaee?nii? i?e?iia?ooc?eii? nenoaie aie?eaoe??
ciai?oiueiee?oeiieo ?ic/ei?a. Iaeei ioa?? -eai?ey?a aeei?enoiaoaaee aeey
i?eeeaaeaiiy oano-?ic/eio, a ae?oaee – aeey i?eeeaaeaiiy ?iaeeoa?aioiiai
?ic/eio. Iao/-i?iaoea c ee?oeiith ciaoiaeeeany a eiio?ieueiiio ?ic/ei? a
aaciina?aaei?e aeecueeino? a?ae a?aieoe? ci?ooaaiiy ?ic/ei?a. Eaia?a
iino?eii ia?oocoaaeany eiio?ieueiei ?ic/eiii aeey caiia?aaiiy
iaeiie/aiith oa?iaeieia?/ieo aaaioia. Aie?eaoe?y cae?enithaaeany i?e
oaeaeeiio cnoa? iaae? i?ae ?ic/eiaie a?aeiinii iao/-i?iaoee i?ae ae??th
i’?ciaeaeo?e/iiai ea?oth/iai i?eno?ith.

aaaioia. E?i/ee iao/-i?iaoee ?icoaoiaoaaee aaciina?aaeiuei a?ey iaae?,
aea noeeaeenue aeaa ?ic/eie, ui i?iioneaeenue. Oaeaeea ci?ia ?ic/eio
aeinyaaeany ia?ai?uaiiyi a?aieoe? i?ae ?ic/eiaie a?aeiinii iao/-i?iaoee
a ?acoeueoao? i?eeeaaeaiiy iiooiaoo iai?oae ia i’?ciaeaeo?e/iee
ia?aieea/. Oey i?ioeaaeo?a aeicaieyea aeinyaoe iiaiiai iai?io ?ic/ei?a
i?ioyaii 0.5 in, ui aeecueei aei ioe?iee i?i?iaeueiiai iiaeeeaiai /ano
iai?io (Maconochie & Knight, 1992). Oaeaee?noue oa aoaeoeai?noue iai?io
?ic/ei?a oanooaaeeny iai?ee?ioe? aenia?eiaioo ca aeiiiiiaith “caeoaaiiy”
eeioeie oa aei??thaaiiy oaeaeeino? ci?ie ??aeeiiiai eiioaeoiiai
iioaioe?aeo c aeei?enoaiiyi ?icaaaeaiiai a 10 ?ac?a eiio?ieueiiai
?ic/eio (Maconochie & Knight, 1992).

Aeaeo?io?c?ieia?/i? aei??thaaiiy. Aioo??oiueiee?oeii? ?ic/eie i?noeee a
nia? (a iI ia 1 e): ?ic/ei 1) EF – 100; o?en-Nl – 30 (?I 7.3); ?ic/ei 2)
EI2?I4 – 100; aetheica – 0.25; IgNl2 – 0,2; IA?AS-o?en – 20; ATP — 5;
GTP — 0.5; (?I 7.3). Ciai?oiueiee?oeii? ?ic/eie i?noeee a nia? (a iI ia
1 e): 1) KCl — 20; NaCl, a?ae 130 aei 0; CaCl2 — 2.5; Tris-Cl — 20 (pH
7.3); 2) KCl, a?ae 0 aei 80; NaCl — 70; CaCl2 — 2.5; Tris-Cl — 20. Ci?ie
a eiioeaio?aoe?? KCl ? NaCl caaaeaee eiiiainoaaeeny aea?iiey?iith
cai?iith ia oie?i-oei?eae.

No?oie ?a?no?oaaeeny ca aeiiiiiaith noaiaea?oii? iaoiaeeee iao/-eeaii o
eiio?ao?aoe?? “oe?ea ee?oeia”. O ?iaio? aeei?enoiaoaaany i?aeneethaa/
aeey iao/-eeaii ae?iaieoeoaa “List Electronics” (O?I). Iao/-i?e?ii?iaoee
c i’yeiai neea iaee ii?? a?ae 0.5 aei 2.0 IIi. Eiiaiaei? c?ooaiiy
iioaioe?aeo ei?eaoaaeeny c o?aooaaiiyi ??aeeiiiai eiioaeoiiai
iioaioe?aeo i?ae aioo??oi?i oa iieaath/ei ?ic/eiaie. A?aeaaaeai? no?oie
o?eueo?oaaeenue (/anoioa c??co 3 eAoe), ioeeo?iaoaaeenue c ?ioa?aaeii
aeene?aoecaoe?? 200 ien, iaeiie/oaaeenue oa aiae?coaaeeny ca aeiiiiiaith
eiii’thoa?a c aeei?enoaiiyi i?ia?aiiiai caaacia/aiiy Irigin (“I?nriNa1”,
NOA). sseui ia cacia/aii ?ioa, aenia?eiaioe aeeiioaaeeny i?e e?iiaoi?e
oaiia?aoo?? (19 – 24 iN).

?ACOEUeOAOE AeINE?AeAEAIUe

I??ai?aei? iae?iie ?aaaothoue ia no?eaeiiiae?aio ci?io
ciai?oiueiee?oeiiiai K+ iia?eueiei ao?aeiei no?oiii. ?aaeoe?y iae?iia
Io?e?i’? ia cnoa ciai?oiueiee?oeiii? eiioeaio?aoe?? eae?th a?ae 0 iI aei
20 iI [K+]out i?iaeaiiino?iaaia ia ?en. 2A. Iiae?ai? a?aeiia?ae?
niinoa??aaeeny o an?o aeine?aeaeaieo Io?e?i’? iae?iiao

?en. 2. ?aaeoe?y iae?ii?a ??cieo oei?a ia no?eaeiiiae?aia ca?eueoaiiy
ciai?oiueiee?oeiiiai eae?th. A. Iae?ii Io?e?i’? ciaoiaeeany a
aaceae??aiio ciai?oiueiio ?ic/ei? ? iio?i oaeaeei ia?aiineany a ?ic/ei c
20 iI KCl. Eae?e i?eeeaaeaee i?e ??cieo cia/aiiyo i?aeo?eiiaaiiai
iioaioe?aeo, a?ae -40 iA aei -100 iA c 10 iA ?ioa?aaeaie, ui aeeeeeaei
«i?yiieooiee» ao?aeiee no?oi. A. I?eeeaae aenia?eiaioaeueieo e?eaeo,
io?eiaieo a iiae?aiiio aenia?eiaio? ia iae?ii? DRG. A, A. Aiaeia?/i?
aenia?eiaioe aoee i?iaaaeai? c a?iieaiiaeueieie (A) ? ei?o?eaeueieie (A)
iae?iiaie. Oaeaeea ca?eueoaiiy ciai?oiueiee?oeiiiai eae?th aeeeeeaei
aeaioaciee ao?aeiee no?oi c aeiaeaoeiaith oiia?eueiaiith eiiiiiaioith,
ui caeaaeaea a?ae iioaioe?aeo. Iino?eia /ano, io?eiaia i?e VH = -100 iA
a (A), aei??aithaaea 34 in.

(n = 8) ? a ia?eoa??eieo iae?iiao (n = 10) ?cieueiaaieo c DRG (?en.
2A). Oaeee eaac?-ieoo?aee ?icaeoie ao?aeiiai no?oio a?aeiia?aea?
eeane/i?e ci?i? «aeoieo» (Halliwell & Adams, 1982; Brown, et al. 1990) o
a?aeiia?aeue ia oaeaee? ci?ie o ciai?oiueiee?oeii?e eiioeaio?aoe??
eae?th. Oaeaee?noue ci?ie ciai?oiueiee?oeiii? eiioeaio?aoe?? K+ ia
aeicaiey? aecia/eoe /aniaee o?ae oeueiai i?ioeano. sse?nii ?ioa ?aaeoe?y
niinoa??aaeany a a?iieaiiaeueieo (?en. 2A) aai ei?oeeaeueieo (?en. 2A)
i??ai?aeieo iae?iiao. No?eaeiiiae?aia ci?ia [K+]out aaaea aei iiyae
ao?aeiiai no?oio, ui iia?eueii aeoeao?oueny, aeyaey?
iioaioe?ae-caeaaei?noue ? cieea? c aeaiiey?ecaoe??th. Oeae no?oi,
iicia/aiee ieae/a ye IK, aeae? aea/aany ia i??ai?aeieo iae?iiao
a?iieaiia uo??a. sse iieacaii a ?en. 2A, ?aaeoe?y iae?iia ia
eiioeaio?aoe?eiee eae??aee ?iioeuen i?e i?aeo?eioaaiiio iioaioe?ae? VH =
-40 iA oyaey? niaith ao?aeiee no?oi, ui ieoo?ai aeoeao?oueny. *an,
i?ioyaii yeiai no?oi, ui aei??th?oueny i?e oeueiio iioaioe?ae?, aeinyaa?
noaoe?iia?iiai ??aiy, aoa i?eeiyoee ye aa?oiy ioe?iea /ano anoaiiaeaiiy
iiai? eiioeaio?aoe?? K+.

Caeaaei?noue no?oio, ui aeoeao?oueny eae??i, a?ae ciai?oiueiee?oeiii?
eiioeaio?aoe?? eae?th. Aiie?ooaea IK caeaaeeoue a?ae ciai?oiueiee?oeiii?
eiioeaio?aoe?? eae?th, a oie /an ye e?iaoeea i? (?en. 3A). ?en. 3A
aeaiiino?o? aenia?eiaio, a yeiio IK aeoeaoaaany aeaiia niiniaaie:
nii/aoeo, cnoaii a?ae 0 aei 20 iI [K+]out ? iio?i a?ae

?en. 3. Aieea ciai?oiuei-ee?oeiii? eiioeaio?aoe?? eae?th ia no?oi, ui
aeoeao?oueny eae??i. A. E?ea? no?oi?a, aeeeeeaieo o a?aeiia?aeue ia
eiioeaio?aoe?eiee no?eaie a?ae 0 iI [K+]out aei ??cieo cia/aiue
eiioeaio?aoe?? K+out. Ieoo?aee ao?aeiee no?oi noi?i-aiaeeoueny
iia?eueiith ?aeaenaoe??th, aiie?ooaea yei? iiiioiiii ca?eue-oo?oueny ?c
c?inoaiiyi eiioeai-o?aoe?? K+out, a oie /an ye e?iaoeea ia caeaaeeoue
a?ae [K+]out. A. Aianie iia?eueii? eiiiiiaioe a caaaeueiee iaia?aiiue
no?oi iaioa? ?c ca?eueoaiiyi ii/aoeiai? eiioeaio?aoe?? K+out. VH = -100
iA.

4 iI aei oiai ae naiiai ??aiy 20 iI. A?aeiia?aeue ia eiioeaio?aoe?eio
noiaeeieo 4-20 iI a?ae??ciy?oueny a?ae 0-20 iI ii aiie?ooae? «ieoo?aiai»
cnoao, yeee noi?iaiaeeoueny o??th ae naii? iacaeaaeiith a?ae
eiioeaio?aoe?? e?iaoeeith. I/aaeaeii, ii/aoeiaee ieoo?aee no?oi
a?aeia?aaea? /anoeio eaiae?a, aeoeaiaaieo iiia?aaeiueith
eiioeaio?aoe??th E+out ? aeicaiey? aecia/eoe e?eao aeoeaaoe?? IK. O
aenia?eiaio?, ui aeaiiino?o?oueny ia ?en.4

?en. 4. E?eaa aeoeaaoe?? IK. A. ?aeaenaoe?? no?oi?a o a?aeiia?aeue ia
oaeaeeo ci?io ?ic/ei?a io?eiai? aeiaeaoeii 80 iI [K+]out ia oii? ??cieo
ii/aoeiaeo eiioeaio?aoe?e ciai?oiueiee?oeiiiai eae?th. VH = -120 iA.
Noaia aei??thaaiue cia?aaeaia ia anoaaoe?. No?oi aeinyaaa noaeiai
cia/aiiy a [K+]out = X iI ? iio?i aiie?ooaea, ui caeaaeeoue a?ae /ano,
aei??thaaeany i?ney no?eaeiiiae?aiiai cnoao aei 80 iI [K+]out.
Iaeneiaeueiee IK aoa aecia/aiee ye iia?eueiee no?oi, aeoeaiaaiee cnoaii
a eiioeaio?aoe?? eae?th a?ae 0 aei 80 iI. A. Noaoe?iia?ia aeoeaaoe?y IK
ciai?oiueiee?oeiiei eae??i.

no?oi aeinyaaa noaoe?iia?iiai ??aiy i?e ??cieo cia/aiiyo ii/aoeiai?
eiioeaio?aoe?? K+out ? iio?i aei??thaaeany aiie?ooaea IK i?ney cnoao aei
iaei??? ? o??? ae aeniei? eiioeaio?aoe?? iiaeeco iane/aiiy aeoeaaoe??
IK, a naia 80 iI. Aenia?eiaioaeuei? aeai? aoee iaaeeaeai? ??aiyiiyi: I /
Imax = 1 / 1 + ([K+]out / IC50) p c? cia/aiiyie IC50 = 2.34 0.31 iI
aeey eiinoaioe iai?aaeoeaaoe?? ciai?oiueiee?oeiiei eae??i ? p = 0.76
0.07 (?en. 4A; n = 5).

Iioaioe?aecaeaaei?noue IK. Iioaioe?aecaeaaei?noue IK i?iaeaiiino?iaaia
ia ?en. 5. Iia?eueiee ao?aeiee no?oi ia ?aaa?noaaa i?e iioaioe?aeao
a?eueo iiceoeaieo, i?ae ??aiiaaaeiee iioaioe?ae aeey ?ii?a eae?th, EK.
Oeae oaeo ?ethno?o?oueny ia ?en. 5A: aeey ciai?oiueiee?oeiii?
eiioeaio?aoe?? eae?th [K+]out = 20 iI eae??aee ??aiiaaaeiee iioaioe?ae,
ia?aaeaa/aiee c ??aiyiiy Ia?inoa aoa ??aiee -40.5 iA ([K+]out /
[K+]in =

?en. 5. Iioaioe?ae-caeaaei?noue IK. A. I?eeeaaeaiiy aeniei?
eii-oeaio?aoe?? eae?th i?e ??cieo VH a?ae -20 iA aei -120 iA c 20 iA
?ioa?aaeaie. IK niinoa??aa?ony o?eueee i?e iioaioe?aeao a?eueo
iaaaoeaieo, i?ae EK. E?iaoeea IK ia caeaaeeoue a?ae iioaioe?aeo.
Iino?ei? /ano aei??aiththoue 76.3 in, 72.9 in, 69.4 in ? 75.1 in aeey
iioaioe?ae?a -120 iA, -100 iA, -80 iA ? -60 iA a?aeiia?aeii. Ia ieaei?e
iaiae? i?aaenoaaeai? ii?iiaai? e?ea?. A. Aieueo-aiia?ia caeaaei?noue IK,
aeeee-eaiiai no?eaeiiiae?aiei ca?eue-oaiiyi eiioeaio?aoe?? eae?th a?ae 0
aei 20 iI () ? aei 80 iI (). A. Iioaioe?ae-caeaaei?noue IK i?e aeaio
??cieo cia/aiiyo [Na+]out: 40 iI () ? 130 iI (). Iniiey?i?noue
i?aeo?eioaaeany cai?iith oei?eaeo iao??th ia oie?i oei??ae.

= 20 / 100), a oie /an ye aeey [K+]out = 80 iI oey aaee/eia aoea ??aia
-5.6 iA. Cia/aiiy iioaioe?aeo, i?e yeiio iia?eueia eiiiiiaioa
eae?e-aeoeaiaaiiai no?oio cieeaea, ca?aaeiny c iioaioe?aeii ?aaa?n??
aeey ?ii?a eae?th (n = 19) oa o ?ac? aa??thaaiiy ??aiy
ciai?oiueiee?oeiiiai eae?th ci?uoaaeinue a?aeiia?aeii aei ci?i EK, ye
iaei aooe o aeiaaeeo oeiiaiai no?oio aioo??oiueiai aei?yieaiiy (Jan &
Jan 1997; Sakmann & Trube, 1984). ?enoiie 5A oaeiae aeaiiino?o?, ui
aiie?ooaea IK ca?eueooaaeany ?c ca?eueoaiiyi ciai?oiueiee?oeiii?
eiioeaio?aoe?? Na+. Iaeiae oea ca?eueoaiiy aiie?ooaee ia noi?iaiaeeeiny
cnoaii iioaioe?aeo, i?e yeiio IK cieeaa.

O/anoue ciai?oiueiee?oeiiiai Na+ a oi?aae?ii? i?ia?aei?noth, ui
aeoeao?oueny eae??i. IK aeoeao?oueny o?eueee a i?enooiino? Na+ o
ciai?oiueiio ?ic/ei?. ?enoiie 6A aeaiiino?o?, ui cai?ia
ciai?oiueiee?oeiiiai Na+ ia oie?i oei?eae aai Li+ aaaea aei cieeiaiiy
iia?eueii? e?iaoeee. No?oi o a?aeiia?aeue ia ca?eueoaiiy
ciai?oiueiee?oeiii? eiioeaio?aoe?? eae?th, ui aei??thaaany a iao???aiio
ciai?oiueiee?oeiiiio ?ic/ei?, aoa a?eueoei i?ae no?oi ui aei??thaaany a
oie?i oei?eae?, aea iaiueoei, i?ae a e?o??aiio ciai?oiueiee?oeiiiio
?ic/ei?. Aeiaeaoie ciai?oiueiee?oeiiiai K+ ia oii? ca?eueoaiiy
eiioeaio?aoe?e ciai?oiueiee?oeiiiai Na+ aeaiiino?o? Na+-caeaaeio iiyao
iia?eueii? e?iaoeee (?en. 6A), a oie /an ye caaaeueia aiie?ooaea no?oio,
ui aeoeao?oueny eae??i, o?eueee o?ioe ca?eueoo?oueny ?c ca?eueoaiiyi
[Na+]out. *aniaee o?ae aeoeaaoe?? IK aeyaeya iiiiaeniiiaioe?aeueio
caeaaei?noue a?ae [Na+]out: eiinoaioa /ano ca?eueooaaeany ?c
ca?eueoaiiyi [Na+]out. E?eaa aeica-a?aeiia?aeue c IC50 = 29.74 3.37 iI
? p = 1.69 0.29 iieacaia ia ?en. 6A (n = 11, A1 = 0.16 e A2 = 1).

?en. 6. IK aeoeao?oueny o?eueee a i?enooiino? Na+ o ciai?oiueiio
?ic/ei?. A. Cai?ia Na+out ia oie?i oei?eae aai Li+ i?eaiaeeea aei
iiaiiai cieeiaiiy IK. VH = -120 iA. A. IK aei??thaaany ia oii? ??cieo
eiioeaio?aoe?e ciai?oiuei-ee?oeiiiai Na+.. E?iaoeea aeoeaaoe?? IK
caeaaeeoue a?ae eiioeaio?aoe?? ciai?oiueiee?oeiiiai iao??th: iino?ei?
/ano aei??aiththoue 36.3 in, 62.2 in, 96.7 in ? 106.5 in aeey [Na+]out =
10 iI, 20 iI, 80 iI ? 130 iI a?aeiia?aeii. Ii?iiaai? e?ea? i?aaenoaaeai?
ia ieaei?e iaiae? A. Aeica-caeaaei?noue aeey IK a?ae ciai?oiueiee?oeiii?
eii-oeaio?aoe?? Na+.

Iniaeeaino? aieeao ?ii?a iao??th ia iaoai?ci aeoeaaoe?? IE. Oaeei /eiii,
ciai?oiueiee?oeiiee Na+ a?a? iiaea?eio ?ieue a ?aaeoe?? i??ai?aeieo
iae?ii?a aei i?aeaeuaiiy ciai?oiueiee?oeiii? eiioeaio?aoe?? K+: ?iie
iao??th caaacia/othoue iia?eueio aeoeaaoe?th no?oio ? ?iaeyoue aianie a
noaoe?iia?io aiie?ooaeo oieo.

Ianooiiee aenia?eiaio aoa i?iaaaeaiee aeey oiai, uia aeaoaeuei?oa
iiynieoe oe? iniaeeaino? aieeao ?ii?a iao??th ia iaoai?ci aeoeaaoe?? IE
(?en. 7). No?eaie ciai?oiueiee?oeiii? eiioeaio?aoe?? eae?th aoa
c?iaeaiee a ?ic/ei?, ui i?noeoue 0 iI [Na+]out, a iio?i Na+out
i?eeeaaeaee o iiiaioe, a?aeiia?aei? ??ciei ia??iaeai ?icaeoeo IK.
?acoeueoaoe oaeeo aenia?eiaio?a, c?iaeaieo i?e iioaioe?ae? VH = -120 iA
(ieaeiy ia?a iaeeaaeaieo e?eaeo) aeacothoue ia oa, ui o a?aenooiino?
?ii?a Na+ any i?ia?aei?noue, ui aa?a o/anoue a iia?euei?e aeoeaaoe?? IK
iiai?noth aeoeaiaaia aai aeoeaaoe?y ciai?oiueiee?oeiiei K+
a?aeaoaa?oueny c aeoaea oaeaeeith e?iaoeeith. Aiaeia?/i? aei??thaaiiy,
i?iaaaeai? i?e ??cieo cia/aiiyo iioaioe?aeo (iieacai? o?eueee -40 iA ?
-20 iA), oaeiae i?iaeaiiino?oaaee, ui iioaioe?ae ?aaa?n?? aeey no?oio,
ui aeeeeeaiee aie?eaoe??th [Na+]out a?aeiia?aea? cia/aiith eae??aiai
??aiiaaaeiiai iioaioe?aeo EK = -40.5 iA ([K+]in / [K+]out = 100 / 20),
ui iiaeia aoei a iiynieoe ?aaoethth/ith ?ieeth ?ii?a Na+ o
ciai?oiueiee?oeii?e na?aae? a iaoai?ci? i?ia?aeiino?, ui aeoeao?oueny
ciai?oiueiee?oeiiei K+.

?enoiie 8A iiynith? aeiaeaoeia? iniaeeaino? ?ie? ?ii?a iao??th. Na+out
aoa aeaeaeaiee ia ??cieo noaae?yo ?icaeoeo IK i?e ??cieo cia/aiiyo
i?aeo?eiiaaiiai iioaioe?aeo. Ci?ie a aiie?ooae? no?oio, ui aeoeao?oueny
eae??i, aeeeeeai? aeaeaeaiiyi ciai?oiueiee?oeiiiai iao??th ?aaa?nothoue
aeecueei aei EK = -17.5 iA ([K+]in / [K+]out = 100 / 50). sse iieacaii
aeey ii??aiyiiy ia ?en. 8A, a?aeiia?ae?, aeeeeeai? aeaeaeaiiyi
ciai?oiueiee?oeiiiai iao??th a ?ic/ei?, ui i?noeoue 0 iI [K+]out cia/ii
iaio?. Oe? aeai? ua ?ac iieacothoue, ui o/anoue Na+out a IK ye iin?y
ca?yaeo iacia/ia: oaeaeoa ?iie iao??th ?aaoeththoue a?aeiia?aeio K+
i?ia?aei?noue, ine?eueee ?aaa?n?y no?oio o a?aeiia?aeue ia
aeaeaeaiiy/aeiaeaiiy Na+out cnoaa?oueny a?aeiia?aeii aei ??aiyiiy
Ia?inoa aeey ?ii?a eae?th (aeea. ?en. 7 ? 8A). Oeae aeniiaie aeia?a
ocaiaeaeo?oueny c aeaieie, ui aeaiiino?othoueny ia ?en. 5A.

?en. 7. Aeey aeoeaaoe?? IK ciai?oiueiee?oeiiee iao??e iiaeiai aooe
i?eeeaaeaiee aei aie?eaoe?? eae?th. Aa?oiy iaiaeue yaey? niaith
caaaeueiee eiioeaio?aoe?eiee i?ioieie aeey [K+]out ? aeaa ??cieo
i?ioieiee aeey [Na+]out. Eiio?ieueiee IK (i?ioieie 1, oiie? e?i??) aoa
io?eiaiee i?e iino?ei?e eiioeaio?aoe?? [Na+]out = 130 iI. I?ioieie 2
(aee?i? e?i??) ?ethno?o? ?acoeueoao aeiaeaoeo Na+ ia ??cieo noaae?yo
?icaeoeo IK. Iia?eueia e?iaoeea IK, ca?a?no?iaaia i?e iioaioe?ae? -120
iA a iao???, i?eaaaeaia ia oii? i?yiieooii? a?aeiia?ae?, io?eiaii? a
?ic/ei?, ui i?noeoue 0 iI [Na+]out. Iiaeaeueo? ei?ioe? aie?eaoe??
[Na+]out aieoue aeinyaathoue noaoe?iia?ii? aiie?ooaee no?oio. ?iioeuene
iao??th a i?ioieie? 2 iathoue o?eaae?noue 30 in. Ci?ie a eiioeaio?aoe??
Na+out eiiiainoaaeeny aea?iiey?iith cai?iith ia oie?i oei?eae.
Aiaeia?/i? aei??thaaiiy aoee oaeiae c?iaeai? i?e iioaioe?aeao VH = -40
iA ? -20 iA.

E?iaoeea IK a?aeia?aaea? ne?aeia? i?ioeane, iia’ycai? c aeiaeaiiyi /
aeaeaeaiiyi Na+ o ciai?oiueiee?oeii?e na?aae?. ?ioa aaaeeeaa
iniaeea?noue, i?aaenoaaeaia ia ?en. 8A: eiee Na+out aeaeaeaiee c
ciai?oiueiee?oeiii? na?aaee, IK ia ia?aoiaeeoue a noai, ui aeoeao?oueny
ieoo?ai — a?i i?iaeiaaeo? iia?eueiee ?icaeoie, oi/ e?iaoeea noa?
oaeaeoith. Oeae oaeo aeaoaeueii aeaiiino?o?oueny ia ?en. 8A: Na+out
aeaeaeaiee /a?ac 15

?en. 8. Aea/aiiy ?ie? Na+ a oi?aae?ii? i?ia?aei?noth IK. A. Na+out a
cia/ii a?eueo?e i??? ?aaoeth? K+-aeoeaiaaio K+ i?ia?aei?noue, i?ae aa?a
o/anoue a iaia?aii?e i?ia?aeiino? ye iin?e ca?yaeo. Oaeaee? aeaeaeaiiy
Na+ aoee c?iaeai? ia ??cieo noaae?yo ?icaeoeo IK. No??eea aeaco? ia
eiio?ieueiee no?oi, aeeeeeaiee 0 — 50 iI cnoaii a [K+]out , [Na+]out =
70 iI, VH = -120 iA. A. A?aeiia?ae?, aeeeeeai? aeaeaeaiiyi
ciai?oiueiee?oeiiiai iao??th, a ?ic/ei? c 0 iI [K+]out ii??aiyii iae?.
(A), (A) — iaeei ? oie naiee iae?ii. A. Iia?eueia e?iaoeea IK noa?
oaeaeeith, aea ia «ieoo?aith» i?ney oaeaeeiai aeaeaeaiiy Na+out.

in i?ney ii/aoeo aie?eaoe?? aeniei? eiioeaio?aoe?? K+out ? IK
i?iaeiaaeo? ?icaeoie c = 25.5 in, a oie /an ye a eiio?ie? = 65.6 in.
Ine?eueee a 0 iI [Na+]out IK ?icaeaa?oueny oaeaeoa, oi ianooiia ca
aeaeaeaiiyi aeiaeaiiy Na+ i?eaiaeeoue aei ia?aneieo eiio?ieueiiai
cia/aiiy IK, ye aeaeii c ii??aiyiiy c eiio?ieai. I?ei?oia oa, ui IK
ii/eia? ne?aeoaaoe eiio?ieuei?e e?iaoeoe? /a?ac aeae?eueea i?e?naeoiae
i?ney oiai, ye Na+out ciiao aeiaeaiee o ciai?oiueiee?oeiio na?aaeo.

Caaaeii, ?enoiie 8 iieaco?, ui ai?ioiee iaoai?ci, eaaea/ee a iniia?
aeoeaaoe?? IK aeiaaa? aeayeiai /ano aeey aeinyaiaiiy noaoe?iia?iiai
noaio a aaciao???aiio na?aaeiaeu?.

Uia ioe?ieoe, ye oaeaeei IK «caaoaa?» Na+out, aoee i?iaaaeai?
aenia?eiaioe (?en. 9), a yeeo IK aeoeaoaaany a aaciao???aiio ?ic/ei? c
?aaoeueiaaiith cao?eieith i?ney aeaeaeaiiy Na+out. «I?ii?aeia» /anoeia
e?iaoeee cieea? i?ioyaii 200 in ( = 46.3 in,

?en. 9. Iaoai?ci i?ia?aeiino?, ui eaaeeoue a iniia? IK iia?eueii
«caaoaa?» ciai?oiueiee?oeiiee Na+. A. Aa?oiy iaiaeue — i?ioieie
aenia?eiaioa ? n?iaenoai e?eaeo. Aie?eaoe?y [K+]out i?iaiaeeeany i?ney
??cieo aeniiceoe?e a ?ic/ei? c 0 iI [Na+]out (TNa+=0). Oea i?eaiaeeei
aei aeieeiaiiy no?oio, yeee aoa a?eueo oaeaeeei, i?ae eiio?ieueiee IK,
(aiaeia?/iee no?oi i?eaaaeaiee ia ?en. 8A, ii??a. (1) ? (2)).
Ca?eueoaiee o?aaiaio i?eaaaeaiee ia na?aaei?e iaiae?. Aiie?ooaea no?oio
ioe?ithaaeany a iiiaio anoaiiaeaiiy eiioeaio?aoe?? K+out i?e
iioaioe?ae?, ia yeiio iia?eueia e?iaoeea aoea a?aenooiueith (-20 iA,
ieaeiy iaiaeue). A. Caeaaei?noue aiie?ooaee a?ae TNa+=0 iaee?auei /eiii
ai?ien?ioaaeanue aeniiiaioe?aeueiith ooieoe??th. A. Iaeii/ania
aie?eaoe?y iao??th ? eae?th ia i?eaiaeeoue aei iia?eueii? e?iaoeee IK.
Iaia?aia iiaeiia anooieoe a eiioaeo c Na+out i?eiaeii? ca 200 in aei
aie?eaoe?? eae?th, uia aeinyaiooe noaoe?iia?ieo oiia.

?en. 9A). Iacia/ia caeeoeiaa eiiiiiaioa «i?ii?aeii?» e?iaoeee
caa??aa?oueny iaa?oue i?e iane?i/aiiiio cia/aii? TNa+=0 = 0 ? iiaea aooe
aeaeaeaia aeaiiey?ecaoe??th (?en. 9A, ieaeiy iaiaeue; aeea. oaeiae ?en.
6A, aeica-a?aeiia?aeue aeey [Na+]out). I?e iaeii/aniiio aeiaeaoeo
iao??th ? eae?th, Na+out ia ni?iiiaeiee niia?eueieoe e?iaoeeo aeoeaaoe??
IK. Iaia?aia iiaeiia anooieoe a eiioaeo c Na+out i?eiaeii? ca 200 in aei
aie?eaoe?? eae?th, uia aeinyaiooe noaoe?iia?ieo oiia (?en. 9A).

E?iaoeea aeoeaaoe?? IK i?iaeaiiino?oaaea aeoaea aenieo oaiia?aoo?io
caeaaei?noue, ye iieacaii aeey eiie?aoiiai iae?iia ia ?enoieo 10 A-A.
Cia/aiiy Q10 ??aia 7.31 0.75 (n = 8) aoei io?eiaii aeey iino?eii? /ano
aeoeaaoe??, a oie /an ye cia/aiiy Q10 = 1.28 0.06 (n = 4) aoei io?eiaii
aeey aiie?ooaee no?oio.

?en. 10. Oaiia?aoo?ia caeaaei?noue e?iaoeee aeoeaaoe?? IK. A. N?iaenoai
no?oi?a aoei io?eiaia ia iaei?e ? o?e aea ee?oei? i?e oaiia?aoo?ao, ui
ci?iththoueny a ae?aiacii? a?ae 10 aei 23OC. A. Cia/aiiy Q10 ??aia 7.94
aoei io?eiaia aeey iino?eii? /ano aeoeaaoe?? o ?ac? eiie?aoiiai iae?iia.
Na?aaei? cia/aiiy Q10 aeey an?o aeaieo — 7.31 0.75 (n = 8). A. Cia/aiiy
Q10 ??aia 1.32 aoei io?eiaia aeey aiie?ooaee IK ia oiio ae naiiio
iae?ii? ui a (A) ? (A). Na?aaei? cia/aiiy Q10 aeey aiie?ooaee — 1.28
0.06 (n = 4).

Oa?iaeieia?/i? aeanoeaino? IK. C iaoith ii??aiyiiy IK c a?aeiieie
eae??aeie no?oiaie, oa?iaeieia?/i? aeanoeaino? eae?e-aeoeaiaaiiai
ao?aeiiai no?oio aea/aeeny i?e i?aeo?eioaaiiio iioaioe?ae? -100 iA. IK
iiai?noth aeieoaaany ciai?oiueiee?oeiiei Ba2+ (5 iI) (?en. 11A) aai TEA
(10 iI) (?en. 11A) aea i?iaeaiiino?oaaa iecueeo /ooeeaenoue aei
ciai?oiueiee?oeiiiai Cs+ (1 iI) (?en. 11A), niaoeeo?/iiai aeieaoi?a
ao?aeiiai no?oio, ui caeaaeeoue a?ae /ano — Ih, yeee ? aeoeaiei a oiio
ae naiiio ae?aiacii? iioaioe?ae?a (Mayer & Westbrook, 1983;
Maccaferry et al.,

?en. 11. Ae?y Cs+ ? Ba2+ ia eae?e-aeoeaiaaiee ao?aeiee no?oi. A. No?oie,
aeeeeeai? nooi?i/anoeie ci?iaie ciai?oiuei? eiioeaio?aoe?? E+ o eiio?ie?
oa o i?enooiueino? 1iI Cs+ oa 1 iI Ba2+. A. Aeica-caeaaei?noue
aeieoth/o? ae?? ciai?oiueiee?oeiiai Ba2+ ia eae?e-aeoeaiaaiee ao?aeiee
no?oi. A. No?oie, aeeeeeai? nooi?i/anoeie ci?iaie ciai?oiuei?
eiioeaio?aoe?? E+ a?ae 0 iI aei 20 iI o eiio?ieueiiio ?ic/ei? oa o
i?enooiueino? 1 oa 10 iI ciai?oiueiee?oeiiiai OAA.

1993)‘‘. IC50 aeey aeieoth/o? ae?? ciai?oiueiee?oeiiai Ba2+ neeaaeaea
480 ?M ± 90 ?M (n = 3) (?en. 11A). Cai?ia K+ ia Cs+ a aeaeiiey?iuo
eiioeaio?aoe?yo o aioo??oiueiee?oeiiiio ?ic/ei? ia aiineea i?yeeo ci?i a
aiie?ooaeo IK. Oaeiae eae?e-aeoeaiaaiee ao?aeiee no?oi ia aeieoaaany
4-ai?iii???ae?iii (4 — AP) a eiioeaio?aoe?? 1 iI, a?aeiiei aeieaoi?ii K+
eaiae?a, ui naeaeoeaii aeieo? ID (Storm, 1993; Crepel et al., 1993) ? IA
(Numann et al., 1987; Rudy, 1988)‘‘‘. IK a?ae??ciyany ii oa?iaeieia?/ieo
aeanoeainoyo a?ae IM, iia?eueiiai no?oio, ui ia ?iaeoeao?oueny (Brown &
Adams, 1980; Storm, 1993)‘‘ ? aoa ia/ooeeaee aei aaii?noo ionea?eiiauo
?aoeaioi??a — ea?aaoieo (50 iM). IK aoa oaeiae ia/ooeeaee aei 1 ?I
oao?iaeioieneio (TTX) ? aei 1 iI oaaa?io, niaoeeo?/iiai aeieaoi?a
N+/K+-ATPace. Ci?ie o eiioeaio?aoe?? ciai?oiueiee?oeiiiai Mg2+ c 0 iI
aei 2.5 iI ia a?aeaeaaeeny ia IK. Aeiaeaiiy ATP o aioo??oiueiee?oeiiee
?ic/ei ia aieeaaei iii?oiei /eiii ia iiaaae?ieo IK. Iia?eueiee no?oi, ui
aeoeao?oueny eae??i, i?aeoe/ii ia aeyaeya run-down a oiae? 1-2 aiaeeiieo
aenia?eiaio?a. IK aoa ia/ooeeaee aei 1 iI ciai?oiueiee?oeiiiai Cd2+.
I?aeaeuaiiy ciai?oiueiee?oeiiiai Ca2+ c 2.5 iI aei 10 iI ia aieeaaei ia
IK.

Iaaiai?aiiy ?acoeueoao?a aeine?aeaeaiue

Ia?aaaaeaiiy K+ i?ia?aeiino? a oi?ioaaii? iioaioe?aeo niieith iae?iiii?
iaia?aie caeaa?eueoiai a?aeaoaa?oueny caaaeyee ?nioaaiith ianeaieo
eaiae?a “aeoieo» (Halliwell & Adams, 1982; Brown et al., 1990), oi/
/enei aeyaeaieo iaoai?ci?a i?ia?aeiino?, a?aeiia?aeaeueieo ca iiaaae?ieo
ee?oei a i?aeii?iaiaiio ae?aiacii? iaia?aiieo iioaioe?ae?a iino?eii
ca?eueoo?oueny, iniaeeai o ?ac? oeaio?aeueieo iae?ii?a. Oe? iae?iie
a?ae??ciythoueny iaaecae/aeii u?eueiei niaeoaaiiyi. An? ci?ie a
o?ainiaia?aiieo ?iiieo a?aae??ioao, aeeeeeai? iae?iiaeueiith aeoeai?noth
i?eaiaeyoue aei aea?eueiaiiy ?ii?a eae?th c aioo??oiueiee?oeiiiai
i?inoi?o ? eiai aeoioethaaiiy a iaaeoi aocueeiio ciai?oiueiee?oeiiiio
i?inoi?? (Sykova, 1983). Iaeiie/aiiy eae?th iiaea aooe ?noioiei /eiieeii
a ?aaoeyoe?? ooieoe?e ia?aiai? nenoaie, oaeeo ye iae?iiaeueia
caoaeaeaiiy ? i?aeee?oeii? aca?iiae??, a oaeiae a ooieoe?iioaaii?
ae?aeueieo ee?oei. Oaeei /eiii, ia aoei aaeeeith ianiiae?aaieith
aeyaeoe, ui cia/ia /anoeia i?ia?aeiino? niieith i??ai?aeieo iae?ii?a,
?icoaoiaaieo a iaea?eueo u?eueii oiaeiaaieo iae?iiaeueieo no?oeoo?ao
caaacia/o?oueny nenoaiith, ui ea?o?oueny iniiaieie i?iieeath/eie ?iiaie
? iai?oaeaiiyi.

Aeine?aee ii aea/aiith aaoa?iaaiiinoe iioaioe?ae?a niieith ano?ioeeo?a a
c??cao aeiieaiia iieacaee caeaaei?noue aeni?an?? eaiae?a aioo??oiueiai ?
ciai?oiueiai aei?yieaiiy a?ae oa?aeoa?o eae??ai? aeoeaiino? a ??cieo
eieaeueieo ciiao (Roy et al., 1996; Janigro et al., 1997). Iiaeia
ia?aaeaa/eoe, ui ee?oeie u?eueii niaeiaaieo iae?iiaeueieo no?oeoo?, ui
caciathoue aenieeo no?eae?a eae?th, oa?aeoa?ecothoueny naeaeoeaiith
aeni?an??th eaiae?a, eaaea/eo a iniia? aeoeaaoe?? IK. I?aeoaa?aeaeaiiyi
oe??? a?iioace iiaea neoaeeoe oie oaeo, ui ?aaeoe?y iae?ii?a Io?e?i’? ?
ia?eoa??eieo iae?ii?a, ?cieueiaaieo c caaei?o ei??ioe?a nieiiiai iiceo,
ia cnoa ciai?oiueiee?oeiii? eiioeaio?aoe?? eae?th (?en. 2 A,A) ye?nii
a?ae??ciy?oueny a?ae ?aaeoe??, ui niinoa??aa?oueny a aeiieaiiaeueieo
(?en. 2 A) aai ei?o?eaeueieo (?en. 2 A) i??ai?aeieo iae?iiao.

Io?eiai? a ?iaio? ?acoeueoaoe aeicaieythoue c?iaeoe i?eiouaiiy, ui ?iie
iao??th ? eae?th a?athoue ?ieue e?aaiae?a aeey niaoeeo?/ieo ae?eueieoeue
c’aycoaaiiy, a?aeiia?aeaeueieo ca noaa?e?caoe?th cia/ii? /anoeie
i?ia?aeiino? niieith i??ai?aeieo iae?ii?a. Aeoiaey/e c eiao?oe??ioa
Oeeea, aeey a?aee?eooy eaiae?a, eaaea/eo a iniia? aeoeaaoe?? IK,
iaiao?aeiee iaeei ?ii K+ (?en. 4A), a oie /an ye aeaa ?iie Na+
iaiao?aei? aeey oiai, uia caaacia/eoe aeinoaoith cao?eieo aeoeaaoe??
oeeo eaiae?a (?en. 6A). Iacaeaaei?noue e?iaoeee aeoeaaoe?? IK a?ae
eiioeaio?aoe?? eae?th aeaco? ia oa, ui c’aycoaaiiy eeaaiaea ia ?
noaae??th, ui aecia/a? oaeaee?noue i?ioeano. E??i eiao?oe??ioa O?ea,
?niothoue ? ?io? oaeoe, aeacoth/? ia ia iaeiicia/io ?ieue ?ii?a iao??th
a ?aaoeyoe?? i?ia?aeiino?, ui aeoeao?oueny eae??i. Oaeaeea aeaeaeaiiy
ciai?oiueiee?oeiiiai Na+ c iiaa?oi? iaia?aie i?eaiaeeoue aei ieoo?aiai
ia?aoiaeo e?iaoeee IK a?ae iia?eueii? aei i?ii?aeii? (?en. 8).
Aiae?coth/e ?acoeueoaoe aeine?ae?a ii aeaeaeaiith/aeiaeaiith
ciai?oiueiee?oeiiiai iao??th iiaeia c?iaeoe i?i?iaeueia i?eiouaiiy i?i
oa, ui iaeei ?ii Na+ ca’yco?oueny c ae?eueieoeyie oaeaeei?
o?ainoi?iaoe?? eaiaeo, a oie /an ye ?ioee caaacia/o? iia?euei?
eiioi?iaoe?ei? ci?ie, ui a?aeaeaathoueny a iia?euei?e e?iaoeoe?
aeoeaaoe?? IE. Ia iiaeia oaeiae aeeeth/aoe iiaeeea?noue oiai, ui
iia?eueia ne??ieaiiy iao??th c iaia?aiieie no?oeoo?aie (?en. 9A, A) ?
ne?aeia? aoaeoe, ui niinoa??aathoueny i?ney eiai aeaeaeaiiy (?en. 9A)
a?aeia?aaeathoue trapping-untrapping, i?ioean oae caaiiai «i?eeeiaiiy —
a?aeeeathaaiiy» ?ii?a, ui a?aeaoaa?oueny a no?oeoo?? eaiaeo. Oey
a?iioaca, i/aaeaeii, iiynith? “?aeaaeuei?» aei?yieyth/? aeanoeaino?
eae?e-aeoeaiaaiiai no?oio, ui ia ?aaa?no? c aeaiiey?ecaoe?th.

sse aoei iieacaii aeua, iaoai?ci, eaaea/ee a iniia? aeoeaaoe?? IK
aeaiiino?o? iniaeeaino? niaoeeo?/iiai ?iiiiai iai?iieea, caeaoiiai ia
o?eueee ?ic??cithaaoe Na+ ? K+, aea oaeiae Na+ ? Li+ (?en. 6A). sse?nia
??cieoey i?ae Na+ ? Li+ a ?o caeaoiino? iiaeoethaaoe K+ i?ia?aei?noue
aoea iienaia aeey TREK-1, iauiaeaaii eeiiiaaiiai eae??aiai eaiaeo (Fink
et al., 1996). O oie naiee /an eaiaee, ui aaciina?aaeiuei aeoeaothoueny
o a?aeiia?aeue ia aeiaeaoie ciai?oiueiee?oeiiiai eae?th, iathoue
oa?aeoa?io oa?iaeieia?th, aeanoeao K+ eaiaeaie, /ooeeaeie aei aeieoth/i?
ae?? TEA ? aa??th. O aeaiee iiiaio aaaeei neacaoe, /e iia’ycaiee IK n Ih
— no?oiii, ui aeoeao?oueny a?ia?iiey?ecaoe??th. Ae?y Cs+ oa Ba2+ (?en.
11) aeaco?, ui oa?iaeieia?/i? aeanoeaino? IK oa Ih aeaui
a?ae??ciythoueny, aea aeey inoaoi/iiai aeniiaeo iaiao?aei? a?eueo
niaoeeo?/i? aeieaoi?e.

Iaaecae/aeii aeniea oaiia?aoo?ia caeaaei?noue e?iaoeee (?en. 10 A-A),
eiia??ii, iiaea iiyniyoueny oei, ui a iniia? aeoeaaoe?? IK eaaeeoue ?yae
ia?aeaeueieo eiioi?iaoe?eieo ci?i. Iauiaeaai? ?iaioe ia a?iieaii?
(Illievich et al., 1994) iieacaee caeaaei?noue aea?eueiaiiy aeooaiaoo
aiane?aeie ?oai?? a?ae oaiia?aoo?e. Aeaye? aeai? aeicaieythoue
ia?aaeaa/eoe caeo/aiiy IK aei oa?ii/ooeeaiai iaoai?cio aea?eueiaiiy
caoaeeeaeo ai?iieeneio. Cie?aia, oaiia?aoo?ia caeaaei?noue
eae?e-aeoeaiaaiiai ([K+]out = 60 iI) aea?eueiaiiy aeooaiaoa iaea
cia/aiiy Q10 = 5.54 a ae?aiaciiao oaiia?aoo? 40 — 34 iC (Dirig et al.,
1997).

O a?iieaii? ei?ioei/ani? ci?ie [K+]i, aeeeeeai? aeaeo?e/iith
noeioeyoe??th eieeaaeeny a?ae ??aiy 2.5 — 3.0 iI aei 12 iI (Krnjevic et
al., 1982). I?aeaeuaiiy eiioeaio?aoe?? eae?th a ?ioa?aae? 6.5 — 8.5 iI
cae?aii ?iaeoeoaaoe yi?e?ioioi?iio aeoeai?noue ye in vivo (Zuckermann &
Glaser, 1968) oae ? in vitro (Rutecki et al., 1985; Traynelis &
Dingledine, 1988; Leschinger et al., 1993). Ciai?oiueiee?oeiia
eiioeaio?aoe?y eae?th i?ae /an ai?eaioeoi?iieo ?ic?yae?a, ui
?a?no?o?oueny in vivo ? i?e ?iaio? ia c??cao iiceo /anoi ia?aaeuo? 10
iI, aeaiiino?oth/e iaeneiaeuei? cia/aiiy a stratim piramidale (Fisher et
al., 1976; Avoli et al., 1996). Io?eiaia aaee/eia IC50 = 2.34 0.31 iI
aeey eiinoaioe iieiaeiii? aeoeaaoe?? ii/aoeiaei ciai?oiueiee?oeiiei
eae??i (?en. 4), ui eaaeeoue a iaeano? o?c?ieia?/ieo eiioeaio?aoe?e
E+out, aiai?eoue i?i iaeneiaeueio aio/e?noue iaoai?cio IK i?e
a?aeoeeaii? [K+]out a?ae ii?iaeueieo cia/aiue. O i??ai?aeieo iae?iiao
CA1 ciie a?iieaiio a ii?iaeueiiio eae?e ([K+]i = 3.5 iI) ei?ioei/aniee
aeaiiey?ecaoe?iee ?iioeuen aeeeeeaa aaia?aoe?th iaeeii/iiai iioaioe?aeo
ae?? (Jensen et al., 1994). I?aeaeuaiiy ciai?oiueiee?oeiii?
eiioeaio?aoe?? eae?th aei 7.5 iI i?ecaiaeeei aei iai?ioiiai aeieeiaiiy
ia/a/ii? aeoeaiino?. Iniiaiith iniaeea?noth aeyaeaiiai iaoai?cio ? oa,
ui iia?eueia aeoeaaoe?y IK iiaeeeaa o?eueee i?e iaia?aiieo iioaioe?aeao
a?eueo iaaaoeaieo, i?ae cia/aiiy EK. Oaea neooaoe?y iiaea aeieeaoe o
?ac? iae?iia, ui iiei?oueny, i?aeaeaiiai oaee? K+, i?aeaeuaiiai
aiane?aeie aeoeaiino? non?aei?o iae?ii?a. Eae?e, ui ei?ioei/anii c??n,
aaia?o? ao?aeiee no?oi, yeee i?aaia ia?aca?yaeeoe i?noe?noue iaia?aie
aei a?eueo aeaiiey?eciaaiiai cia/aiiy iioaioe?aeo niieith. Oiia?eueiaiee
iaoai?ci aeoeaaoe?? i?ia?aeiino?, ui eaaeeoue a iniia? IK, ciaioo? oeae
aioo??oi?e no?oi aeioe, iiee iaia?aiiee iioaioe?ae a?eueo iaaaoeaiee,
i?ae EK. A?aeiia?aeii, ooai?th?oueny iaaaoeaiee cai?ioiee ca’ycie ?
aeaiiey?ecaoe?y, aeeeeeaia i?aeaeuaiiyi ciai?oiueiee?oeiiiai eae?th,
niia?eueith?oueny. Aeno?aiieyoe?y io?eiaieo aeaieo aeey ioe?iee e?iaoeee
IK i?e 37 oC aea? cia/aiiy iino?eii? /ano aeey iia?eueii? aeoeaaoe??
i?ae 3 ? 5 in — ui ii??aiyiii ?c /anii ?icaeoeo iiioeyoe?eiiai niaeea a
stratum pyramidale o a?aeiia?aeue ia noeioeyoe?th stratum radiatim CA1
ciie a?iieaiio (Jensen et al., 1994; Jensen & Yaari, 1997; Poolos et
al., 1987). Oaeei /eiii, aeyaeaiee iaoai?ci iiaea a?aoe aaaeeeao ?ieue a
caiia?aaii? iae?ii?a a?ae niiioaiiiai caoaeaeaiiy, aeeeeeaiiai
i?aeaeuaiiyi ciai?oiueiee?oeiiiai eae?th. Cai?iiiiiaaia ooieoe?y IK
iiaea iaoe cia/aiiy o?eueee a u?eueii oiaeiaaieo iae?iiieo iao?eoeyo,
oaeeo ye a?iieaii aai ei?oaen.

sse aeueoa?iaoeaa, ia iiaeia aeeeth/aoe o/anoue iienaiiai iaoai?cio a
?iiiiai?iieo i?ioeanao. Inoaii?i /anii c’yaeany oe?eee ?yae ?ia?o,
i?enay/aieo ?ie? ciai?oiueiee?oeiiiai eae?th a aeiaaio?eaae?e
GABA-iiina?aaeeiaaii? aeaiiey?ecaoe??, aeeeeeai?e aeniei/anoioiith
noeioeyoe??th i??ai?aeieo iae?ii?a a?iieaiia uo?a. Cie?aia, aoei
iieacaii (Avoli et al., 1996; Kaila, et al., 1997; Lamsa & Kaila, 1997)
ui eieaeuei? aaeuei?ai? ia?aae? a?iieaiiaeueieo iae?ii?a caeaoi?
aaia?oaaoe eae??aee o?aic??io, ui aeinyaa? 5 — 8 iI [K+]out. O
iauiaeaai?e ?iaio? (D’Ambrosio et al., 1998) ia a?iieaiiaeueieo
ano?ioeeoao — ee?oeiao, ui aa?ooue o/anoue a i?inoi?iaiio iaeiie/aii?
[K+]out (Newman, 1995) aoea aeyaeaia iia?eueia i?ia?aei?noue, ui
aeoeao?oueny eae??i, c iecueeith /ooeea?noth aei ciai?oiueiee?oeiiiai
Cs+. sse a a?iieaii?, oae ? a ei?? i??ai?aei? iae?iie aeeth/ai? a
eiiieaenio iae?iiaeueioth ia?aaeo, ?aaoeueiaaio aaaaoinoaae?eieie
i?ioeanaie caoaeaeaiiy oa aaeueioaaiiy. Aeniei/anoioia noeioeyoe?y
i??ai?aeieo iae?ii?a a?iieaiio a i?enooiino? aioaaii?no?a ?iiio?iiieo
aeooaiaoieo ?aoeaioi??a aeeeeea? aeaioeiiiiiaioiee GABA-iiina?aaeeiaaiee
iinoneiaioe/iee iioaioe?ae (Davies & Collingridge, 1993; Staley et al.,
1992; Kaila et al., 1997). Oey a?aeiia?aeue neeaaea?oueny c oaeaeeiai
aeia?iiey?ecaoe?eiiai aaeueiiaiai iinoneiaioe/iiai iioaioe?aeo ?
o?eaaeiai GABA-iiina?aaeeiaaiiai aeaiiey?ecaoe?eiiai iinoneiaioe/iiai
iioaioe?aeo. Oaeei /eiii, aeaiiey?ecaoe?th, ui ?icaeyaeaeany ?ai?oa ye
i?ciy noaae?y iinoneiaioe/iiai iioaioe?aeo, iiaeia ca’ycaoe c? no?eaeii
[K+]o, ui aeeeeeaiee caoaeaeaiiyi noi?aeieo c i??ai?aeieie ee?oeiaie
?ioa?iae?ii?a. Oe? aeai? ia?aaeaa/athoue oi?eaeueio iiaeeea?noue: IK
iiaea aooe caeo/aiee aei oi?ioaaiiy ?aaeoe?? i??ai?aeieo iae?ii?a o
a?aeiia?aeue ia no?eaeiiiae?ai? ci?ie ciai?oiueiee?oeiiiai eae?th, ui
aaia?othoueny aeoeai?noth non?aei?o iae?ii?a. O?c?ieia?/ia ?ieue IK
iiaea aooe a cao?eioe? K+- aeoeaiaaiiai iaae?iiy ao?aeiiai iii?o ?,
a?aeiia?aeii, ooiooaaiiy i?ciueiai iinoneiaioe/iiai aaeueioaaiiy.

AEniiaeE

1. I?e caoaeaeaii? u?eueii niaeiaaieo oeaio?aeueieo iae?ii?a
a?aeaoaa?oueny cia/ia ca?eueoaiiy ciai?oiueiee?oeiii? eiioeaio?aoe??
eae?th (a?ae 2-4 iI aei 5-9 iI). Oe?iei ?iciianthaeaeai? iaoieia??
oeaio?aeueii? ia?aiai? nenoaie noi?iaiaeaeothoueny ua a?eueoeie
cia/aiiyie eiioeaio?aoe?e eae?th (15 iI ? aeua). O c’yceo c oeei, o
aeaii?e ?aaio? aeine?aeaeoaaeeny a?aeiia?ae? ?cieueiaaieo i??ai?aeieo
iae?ii?a ia oaeaeea i?aeaeuaiiy eiioeaio?aoe?? ?ii?a eae?th. Aeine?aee
i?iaaaeai? ?c canoinoaaiiyi iaoiaea iao/-eeaii o eiio?ao?aoe?? “a?ae
oe?ei? ee?oeie”. Oaeineiiaeaiiy oaoi?ee ?iioeuenii? ci?ie ?ic/eio ca
aeiiiiiaith iaoiaeo ia?aieeaiiy iioie?a aeaei iiaeeea?noue ?icae?eeoe
no?oi, ui aeoeao?oueny eae??i ia ie?ai? eiiiiiaioe oa c aaeeeith
oi/i?noth ca?a?no?oaaoe ?o ni?aa?aeiioaiiy.

2. I?aeaeuaiiy ciai?oiueiee?oeiii? eiioeaio?aoe?? ?ii?a E+ aeeeeeaei
aeaioaciee ao?aeiee no?oi i?e iaia?aiieo iioaioe?aeao, iaaaoeai?oeo ca
iioaioe?ae ?aaa?n?? aeey ?ii?a K+. Oeae no?oi neeaaeaany c? no?oio
aeoieo, ui “aieoue“ ci?ith?oueny oa oiia?eueiaiiai no?oio (IK) c = 40 —
50 in i?e 21OC.

3. Niinoa?aaeaiee oiia?eueiaiee no?oi iaa e?iaoeeo aeoeaaoe?? ia?oiai
ii?yaeeo c aeoaea aenieith oaiia?aoo?iith caeaaei?noth (Q10 = 7.31).
Eiai e?iaoeea ia caeaaeaea a?ae iioaioe?aeo ? eiioeaio?aoe?? ?ii?a K+.
Aiie?ooaea oeueiai no?oio aecia/aeany i?eeeaaeaiith eiioeaio?aoe??th
?ii?a K+ oa ca?eueooaaeanue ca oiia a?ia?iiey?ecaoe??.

4. Aianie iia?eueii? eiiiiiaioe a caaaeueiee iaia?aiiee no?oi iaioaa ?c
ca?eueoaiiyi ii/aoeiai? eiioeaio?aoe?? K+out. A?aeiia?aeia
eiioeaio?aoe?y iieiaeiii? ae?? aei??aith? 2.5 iI aeey aeoeaaoe??
ii/aoeiaei ciai?oiueiee?oeiiei eae??i.

5. Iioaioe?ae-caeaaei?noue IK, ui aei??thaaeanue i?e i?aeo?eioaaieo
iioaioe?aeao -120 — -20 iA, aoea iiae?aiith aei iioaioe?ae-caeaaeiino?
E+ no?oi?a ?c aioo??oi?i aei?yieaiiyi.

6. Aeoeaaoe?y IK caeaaeeea a?ae eiioeaio?aoe?? ?ii?a Na+: cai?ia
ciai?oiueiee?oeiiiai Na+ ia oie?i oei?eae aai e?o?e iaeaea iiai?noth
onoaaea IK.

7. IK ia niinoa??aaany a iae?iiao caaei?o ei??ioe?a nieiiiai iiceo oa
iae?iiao iici/ea.

8. Niia?eueithth/e ao?ae E+ a ee?oeio, IK iiaea a?aoe ?noioio ?ieue a
caiia?aaii? u?eueii oiaeiaaieo i??ai?aeieo iae?ii?a a?iieaiio oa ei?e
a?ae niiioaiiiai caoaeaeaiiy aiane?aeie oaeaeeiai i?aeaeuaiiy
ciai?oiueiee?oeiii? eiioeaio?aoe?? ?ii?a E+.

Ia?ae?e iioae?eiaaieo i?aoeue caeiaoaa/a ca oaiith aeena?oaoe??.

1. V. Filippov, V. Pinchenko, T. Volkova and O. Krishtal. Membrane
responses to extracellular potassium in isolated pyramidal neurons //
Neurophysiology. -1998. -V. 30, — N. 4/5. — P. 259-263.

2. V. Filippov, O. Krishtal. Pharmacological properties of potassium
activated inward current in hippocampal pyramidal neurons //
Neurophysiology. -1999. -V. 31, -N. 1. -P. 69-73.

3. V. Filippov, O. Krishtal. The mechanism gated by external K+ and Na+
controls the resting conductance in hippocampal and cortical neurones //
Neuroscience. -1999. -V. 92, -N. 4. -P. 1231-1242.

Oace aeiiia?aeae:

1. O. Krishtal, V. Pinchenko, V. Filippov et.al. K+ activated, K+, Na+ —
permeable inward rectifier in the hippocampal pyramidal neurones // Eur.
J. Neurosci. -1996. -N. 9, -P. 15.

2. V. Filippov, V. Pinchenko, T. Volkova, O. Krishtal. K+, Na+ — gated
inward delayed rectifier in the hippocampal pyramidal neurones // Israel
J. Med. Sci. -1996. -V. 32, -P. 26.

3. V. Filippov, N.Lozovaya, T. Volkova, O. Krishtal. K+-activated
potassium conductance controls the major part of the input resistance of
the hippocampal and cortical neurones // Soc. for Neurosci. Abstracts,
-1997. -N. 23, -P. 1197

4. V. Filippov, O. Krishtal. Slow membrane responses to extracellular
potassium in isolated hippocampal neurones // J. Physiol. -1998. -N.
513P, -P. 132.

Aiioaoe??:

O?e?iia A. I. E+-aeoeaiaaia Na+-ea?iaaia eae??aa i?ia?aei?noue o
iaia?ai? i??ai?aeieo iae?ii?a iiceo uo?a. — ?oeiien.

Aeena?oaoe?y ia caeiaoooy a/aiiai nooiaiy eaiaeeaeaoa a?ieia?/ieo iaoe
ca niaoe?aeueiinoth 03.00.02 — A?io?ceea. — ?inoeooo O?c?ieia?? ?i. I.
I. Aiaiiieueoey, Ee?a, 1999.

Aeena?oaoe?y i?enay/aia aea/aiith ?aaeoe?? aino?i?cieueiaaieo
i??ai?aeieo iae?ii?a ia oaeaeea i?eeeaaeaiiy ?ii?a eae?th ?c
canoinoaaiiyi iaoiaea iao/-eeaii o eiio?ao?aoe?? “a?ae oe?ei? ee?oeie”.
I?aeaeuaiiy ciai?oiueiee?oeiii? eiioeaio?aoe?? ?ii?a E+ aeeeeeaei
aeaioaciee ao?aeiee no?oi i?e iaia?aiieo iioaioe?aeao iaaaoeai?oeo ca
iioaioe?ae ?aaa?n?? aeey ?ii?a K+. Oeae no?oi neeaaeaany c? no?oio
aeoieo oa oiia?eueiaiiai no?oio (IK) c = 40 — 50 in i?e 21OC.
Niinoa?aaeaiee oiia?eueiaiee no?oi iaa e?iaoeeo aeoeaaoe?? ia?oiai
ii?yaeeo, ui ia caeaaeaea a?ae iioaioe?aeo oa eiioeaio?aoe?? ?ii?a K+.
Aiie?ooaea oeueiai no?oio aecia/aeany i?eeeaaeaiith eiioeaio?aoe??th
?ii?a K+ oa ca?eueooaaeanue ca oiia a?ia?iiey?ecaoe??.
Iioaioe?ae-caeaaei?noue IK aoea iiae?aiith aei iioaioe?ae-caeaaeiino? E+
no?oi?a ?c aioo??oi?i aei?yieaiiyi. Aeoeaaoe?y IK caeaaeaea a?ae
eiioeaio?aoe?? ?ii?a Na+; cai?ia ciai?oiueiee?oeiiiai Na+ ia oie?i
oei?eae /e e?o?e iaeaea iiai?noth onoaaea IK.

IK niinoa??aaany a i??ai?aeieo iae?iiao a?iieaiia ? ei?oaena, iaeiae aoa
i?aeoe/ii a?aenooi?e a iae?iiao caaei?o ei??ioe?a nieiiiai iiceo oa
iae?iiao iici/ea. Niia?eueithth/e ao?ae E+ a ee?oeio, IK iiaea a?aoe
?noioio ?ieue a caiia?aaii? u?eueii niaeiaaieo i??ai?aeieo iae?ii?a a?ae
niiioaiiiai caoaeaeaiiy aiane?aeie oaeaeeiai i?aeaeuaiiy ciai?oiuei?
eiioeaio?aoe?? ?ii?a E+.

Eeth/ia? neiaa: a?iieaii, ei?oaen, eae??aay i?ia?aei?noue,
ciai?oiueiee?oeiiee eae?e, iao??e, iaoiae o?enaoe?? eiioeaio?aoe??.

Filippov V. M. E+-activated Na+-gated potassium conductance in isolated
pyramidal neurons of rat. — Manuscript.

Thesis for Ph.D. degree by specialty 03.00.02 — Biophysics. — Bogomoletz
Institute of Physiology, Kiev, 1999.

The dissertation is devoted to investigation of the responses of acutely
isolated pyramidal neurons to rapidly altered external [K+] using the
whole-cell patch clamp and concentration clamp techniques. The
excitation of densely packed mammalian central neurons is followed by a
substantial transitory elevation of external K+ concentration. This
phenomenon may have a different functional significance depending on how
the resting membrane conductance mechanisms react to the changes in the
gradient of these ions. We have found that in the hippocampal and cortex
neurons of rat a large fraction of the membrane conductance in the
vicinity of the resting potential is provided by the K+ permeability
mechanism which is gated by external K+ and Na+.

Elevation of [K+]out induced a biphasic inward current at membrane
potentials more negative than the reversal potential for K+ ions. This
current consisted of an “instantaneously” increased leakage component
and a slowly activated current ( = 40 — 50 ms at 21OC) designated below
as IK. The latter demonstrated a first order activation kinetics with a
remarkably high Q10 = 7.31 (n = 8). Potential at which IK disappeared
was found to be virtually indistinguishable from EK (n = 19).
Qualitatively this voltage was shifted in accordance with the changes in
EK like in the case of a typical inward rectifier. IK was absent in the
peripheral sensory neurons as well as in the Purkinje neurons.

Slow activation of IK was critically dependent on [Na+]out :
substitution of external Na+ with choline chloride or Li+ leads to
disappearance of the slow kinetics. Application of extracellular K+ on
the background of increasing concentrations of Na+ demonstrates a
Na+-dependent appearance of the slow kinetics, while the total amplitude
of the response insignificantly increases with the increase in Na+out
(IC50 = 29.74 3.37 mM and p = 1.69 0.29). The time-course of
activation was apparently monoexponential and concentration-dependent:
its rate increased with the increase in Na+out .

While the gating mechanism of IK channels has the features of a specific
ion-exchanger capable of discriminating not only between Na+ and K+, but
also between Na+ and Li+, the channels themselves have a characteristic
pharmacology of K+ channels sensitive to the blocking action of TEA and
Ba2+. IK was completely blocked by external TEA (10 mM) or Ba2+ (5 mM;
IC50 = 480 iM ± 90 iM) and only slightly affected by 2 mM of Cs+, a
specific blocker of time-dependent inward current Ih which is active in
the same voltage range‘‘. The replacement of K+ with Cs+ in equimolar
concentration in the internal solution caused no obvious changes in the
amplitude of IK. This current was not affected by 1 mM of
4-aminopyridine (4-AP), a K+channel blocker known to selectively inhibit
ID‘ and IA‘‘. IK differs from IM, a slow, non-inactivating current ‘‘in
its insensitivity to muscarinic agonist carbachol (50 M). IK was also
insensitive to 1 M tetrodotoxin (TTX) and to 1 mM of ouabain, a specific
inhibitor of N+/K+ -ATPase. Introduction of ATP into the perfused neuron
did not alter the behaviour of IK. The latter was not subjected to any
significant run-down in the course of 1-2 h long experiments. Elevation
of external Ca2+ from 2.5 mM to 10 mM did not change IK.

It appears that K+ and Na+ play the role of ligands for a specific low
affinity binding sites which are responsible for the regulation of major
part of the resting conductance of pyramidal neurons. Presumably, one
ion of K+ is necessary to open the channels, while two ions of Na+ may
be needed to induce a remarkable delay into the process of channel
activation. The kinetics of this process is independent of K+
concentration indicating that the ligand binding is not a rate-limiting
step.

A specific property of the discovered mechanism is that its slow
activation is possible only at membrane voltages more negative than the
acting value of EK. Such situation can transiently occur in the case of
resting neuron subjected to the wave of increased K+ generated by the
activity of neighbouring neurons. Transiently increased K+ generates the
inward current, which tends to recharge the membrane capacitance to a
depolarized resting potential. The delayed activation of conductance
mechanism underlying IK attenuates this inward current so far as the
membrane potential is more negative than EK. Correspondingly, the
K+-induced depolarization is delayed and the negative feed-back is
introduced. Qualitatively the suggested function of IK may be of
significance only in the tightly packed neuronal matrixes, such as
hippocampal pyramidal layer or cortex. Alternatively, the involvement of
the described mechanism in the ion-exchange processes cannot be
excluded. Slow K+-activated inward current with low sensitivity to
external Cs+ has been recently demonstrated in a group of hippocampal
astrocytes (D’Ambrosio et al., 1998), cells that in general are supposed
to participate in the “spatial buffering” of K+.

Pyramidal neurons are incorporated in a complex network, which exerts
multicomponent excitatory and inhibitory action on each neuron.
Long-lasting depolarization evoked by high frequency stimulation of
hippocampal pyramidal neurons has been detected in the presence of
ionotropic glutamate receptor antagonists (Davies & Collingridge, 1993;
Kaila et al., 1997).‘ Previously considered as a late component of post
— synaptic potential, this depolarization has been attributed now to the
K+ transient generated by the excited interneurons adjacent to the
pyramidal cells (Kaila et al., 1997). Thus, IK may well be involved in
the shaping of the response of the pyramidal neurons to the waves of
external potassium elicited by the activity of neighbouring neurons. Its
role could be in delaying the K+ — induced drop of the input resistance
so that the late post — synaptic inhibition would not be excessively
shunted.

Key words: hippocampus; cortex; potassium conductance; external
potassium; sodium; concentration clamp.

Oeeeiiia A. I. E+-aeoeae?oaiay Na+-oi?aaeyaiay eaeeaaay i?iaiaeeiinoue a
iaia?aia ie?aieaeiuo iae?iiia iicaa e?unu. — ?oeiienue.

Aeenna?oaoeey ia nieneaiea o/aiie noaiaie eaiaeeaeaoa aeieiae/aneeo iaoe
ii niaoeeaeueiinoe 03.00.02 — Aeioeceea. — Einoeooo Oeceieiaee ei. A. A.
Aiaiiieueoea, Eeaa, 1999.

Aeenna?oaoeey iinayuaia eco/aieth ?aaeoeee naaaeaeciei?iaaiiuo
ie?aieaeiuo iae?iiia ia auno?ia i?eeiaeaiea eaeey n eniieueciaaieai
iaoiaea iyo/-eeyii a eiioeao?aoeee “io oeaeie eeaoee”. Iiauoaiea
aiaeeaoi/iie eiioeaio?aoeee eiiia E+ aucuaaei aeaoooaciue aoiaeyuee oie
i?e iaia?aiiuo iioaioeeaeao aieaa io?eoeaoaeueiuo /ai iioaioeeae
?aaa?nee aeey eiiia K+. Yoio oie ninoiye ec oiea ooa/ee e caiaaeeaiiiai
oiea (IK) n = 40 — 50 in i?e 21OC. Iaaethaeaaiue caiaaeeaiiue oie
eeiaoeeo aeoeaaoeee ia?aiai ii?yaeea, eioi?ay ia caaenaea io iioaioeeaea
e eiioeaio?aoeee eiiia K+. Aiieeooaea yoiai oiea ii?aaeaeyeanue
i?eeiaeaiiie eiioeaio?aoeeae eiiia K+ e oaaee/eaaeanue i?e
aeia?iiey?ecaoeee. Iioaioeeae-caaeneiinoue IK auea iiaeiaiie
iioaioeeae-caaeneiinoe E+ oieia aioo?aiiaai aui?yieaiey. Aeoeaaoeey IK
caaeneea io eiioeaio?aoeee eiiia Na+; niaia aiaeeaoi/iiai Na+ ia oieei
oei?eae eee eeoee ii/oe iieiinoueth iiaeaaeyea IK. IK iaaethaeaaony a
eciee?iaaiiuo iae?iiao aeiiieaiia e ei?oaena e i?aeoe/anee ionoonoaoao a
iae?iiao nieiaeueiuo aaiaeeaa e a iae?iiao Io?eeiuea.

Caiaaeeyy aoiae E+ a eeaoeo, IK iiaeao ea?aoue nouanoaaiioth ?ieue a
i?aaeio?aiaiee ieioii oiaeiaaiiuo ie?aieaeiuo iae?iiia io niiioaiiiai
aicaoaeaeaiey a ?acoeueoaoa auno?iai iiauoaiey ia?oaeiie eiioeaio?aoeee
eiiia E+.

Eeth/aaua neiaa: aeiiieaii, ei?oaen, eaeeaaay i?iaiaeeiinoue,
aiaeeaoi/iue eaeee, iao?ee, iaoiae oeenaoeee eiioaio?aoeee.

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